ArticleCancer research2016
Dual Targeting of CDK4 and ARK5 Using a Novel Kinase Inhibitor ON123300 Exerts Potent Anticancer Activity against Multiple Myeloma.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Unveiling the Impact of Copper Metabolism on Epithelial-Mesenchymal Transition of Triple-Negative Breast Cancer: Identification of Therapeutic Targets.Interdisciplinary sciences, computational life sciences · 2026Article
- The long non-coding RNA CRNDE stabilises SIRT1 protein and influences Hedgehog signalling in multiple myeloma.Leukemia · 2025Article
- The Goldilocks paradigm: comparing classical machine learning, large language models, and few-shot learning for drug discovery applications.Communications chemistry · 2024Article
- ARK5 enhances cell survival associated with mitochondrial morphological dynamics from fusion to fission in human multiple myeloma cells.Cell death discovery · 2024Article
- Prevalence and impact of diabetes on survival of patients with multiple myeloma in different racial groups.Blood advances · 2024Article
- NUAK1 coordinates growth factor-dependent activation of mTORC2 and Akt signaling.Cell & bioscience · 2023Article
- Fyn Signaling in Ischemia-Reperfusion Injury: Potential and Therapeutic Implications.Mediators of inflammation · 2022Review
- Mitochondria and Their Relationship with Common Genetic Abnormalities in Hematologic Malignancies.Life (Basel, Switzerland) · 2021Review
- Role of ARK5 in cancer and other diseases (Review).Experimental and therapeutic medicine · 2021Review
- Review
- Knockdown of long non-coding RNA plasmacytoma variant translocation 1 inhibits cell proliferation while promotes cell apoptosis via regulating miR-486-mediated CDK4 and BCAS2 in multiple myeloma.Irish journal of medical science · 2020Article
- A novel role for NUAK1 in promoting ovarian cancer metastasis through regulation of fibronectin production in spheroids.Cancers · 2020Article
- Effect of Gender on the Pharmacokinetics of ON 123300, A Dual Inhibitor of ARK5 and CDK4/6 for the Treatment of Cancer, in Rats.European journal of drug metabolism and pharmacokinetics · 2019Article
- miR-424-5p represses the metastasis and invasion of intrahepatic cholangiocarcinoma by targeting ARK5.International journal of biological sciences · 2019Article
- The potent and selective cyclin-dependent kinases 4 and 6 inhibitor ribociclib (LEE011) is a versatile combination partner in preclinical cancer models.Oncotarget · 2018Article
- A feed forward loop enforces YAP/TAZ signaling during tumorigenesis.Nature communications · 2018Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Multiple myeloma is a fatal plasma cell neoplasm accounting for over 10,000 deaths in the United States each year. Despite new therapies, multiple myeloma remains incurable, and patients ultimately develop drug resistance and succumb to the disease. The response to selective CDK4/6 inhibitors has been modest in multiple myeloma, potentially because of incomplete targeting of other critical myeloma oncogenic kinases. As a substantial number of multiple myeloma cell lines and primary samples were found to express AMPK-related protein kinase 5(ARK5), a member of the AMPK family associated with tumor growth and invasion, we examined whether dual inhibition of CDK4 and ARK5 kinases using ON123300 results in a better therapeutic outcome. Treatment of multiple myeloma cell lines and primary samples with ON123300 in vitro resulted in rapid induction of cell-cycle arrest followed by apoptosis. ON123300-mediated ARK5 inhibition or ARK5-specific siRNAs resulted in the inhibition of the mTOR/S6K pathway and upregulation of the AMPK kinase cascade. AMPK upregulation resulted in increased SIRT1 levels and destabilization of steady-state MYC protein. Furthermore, ON123300 was very effective in inhibiting tumor growth in mouse xenograft assays. In addition, multiple myeloma cells sensitive to ON123300 were found to have a unique genomic signature that can guide the clinical development of ON123300. Our study provides preclinical evidence that ON123300 is unique in simultaneously inhibiting key oncogenic pathways in multiple myeloma and supports further development of ARK5 inhibition as a therapeutic approach in multiple myeloma.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.